Infection by hepatitis C virus (HCV) is a compelling human medical problem. HCV is recognized as the causative agent for most cases of non-A and non-B hepatitis, with an estimated worldwide prevalence of 170 million cases (i.e., 2-3%) (Choo et al., Science, 1989, 244:359-362; Kuo et al., Science, 1989, 244:362-364; Purcell, FEMS Microbiol. Rev., 1994, 14:181-192; Van der Poel, In: Current Studies in Hematology and Blood Transfusion, Reesink ed., Basel: Karger, pp. 137-163, 1994). Four million individuals may be infected in the United States alone (Alter and Mast, Gastroenterol. Clin. North Am., 1994, 23:437-455).
HCV is primarily transmitted parenterally, although sexual and perinatal transmission do appear to occur. At present, no risk factor has been identified in about 40% of HCV-infected individuals in the US (Alter, Infect. Agents Dis., 1993, 2:155-166). Upon first exposure to HCV, only about 10% or less of infected individuals develop acute clinical hepatitis, while others appear to resolve the infection spontaneously. In most instances, however, the virus establishes a chronic infection that persists for decades, leading in about 50% of all cases to chronic hepatitis, which can, in turn, develop into liver cirrhosis and/or hepatocellular carcinoma (Iwarson, FEMS Microbiol. Rev., 1994, 14:201-204; Kew, ibid. pp.211-220; Saito et al., Proc. Natl. Acad. Sci. USA, 1990, 87:6547-6549).
Apart from liver cells, HCV can also replicate in peripheral blood mononuclear cells (PBMCs) both in vivo and in experimentally infected B- and T-cell lines (U.S. Pat. Nos.: 5,679,342 and 5,968,775). Such a lymphotropism may account for the numerous immunological disorders, in particular type II and type III cryoglobulinaemia, observed in more than 50% of chronic hepatitis C patients (Esteban et al., In: Hepatitis C Virus, Reesink ed., Basel: Karge, 1998, pp. 102-118).